THE 2ND ETV6 ALLELE IS NOT NECESSARILY DELETED IN ACUTE LEUKEMIAS WITH A ETV6 ABL FUSION/

The ETV6 (TEL) locus at chromosome band 12p13 is a major site of trans locations in acute leukemia, particularly in childhood acute lymphobla stic leukemia (ALL). In cases with translocations involving ETV6, the normal ETV6 allele is often deleted. In addition, loss of heterozygosi ty of ETV6 is frequently observed in childhood ALL. Thus, it has been suggested that ETV6 may have an anti-oncogenic role to play, in additi on to its oncogenic role. We have described an unusual case of ALL in which ETV6 is found fused to the ABL gene; ABL is normally activated b y fusion to the BCR gene in the 9:22 translocation. We expanded the pr imary cells from this ETV6/ABL rearranged case of ALL in SCID animals and analyzed them for expression of both ETV6/ABL and the normal ETV6 mRNA. We found that both the rearranged and normal ETV6 mRNAs are expr essed in the expanded cell population. Furthermore, sequence analysis of the ETV6 PCR product revealed no point mutations which would influe nce the amino acid sequence. Thus, deletion of the second EN6 allele i s not necessary for the transformation to leukemia by ETV6/ABL. (C) 19 98 Wiley-Liss, Inc.